利用病毒载量和流行动力学在资源受限环境中优化混合检测
Using viral load and epidemic dynamics to optimize pooled testing in resource-constrained settings.
作者信息
Cleary Brian, Hay James A, Blumenstiel Brendan, Harden Maegan, Cipicchio Michelle, Bezney Jon, Simonton Brooke, Hong David, Senghore Madikay, Sesay Abdul K, Gabriel Stacey, Regev Aviv, Mina Michael J
机构信息
Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Centre for Communicable Disease Dynamics, Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
出版信息
Sci Transl Med. 2021 Apr 14;13(589). doi: 10.1126/scitranslmed.abf1568. Epub 2021 Feb 22.
Virological testing is central to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) containment, but many settings face severe limitations on testing. Group testing offers a way to increase throughput by testing pools of combined samples; however, most proposed designs have not yet addressed key concerns over sensitivity loss and implementation feasibility. Here, we combined a mathematical model of epidemic spread and empirically derived viral kinetics for SARS-CoV-2 infections to identify pooling designs that are robust to changes in prevalence and to ratify sensitivity losses against the time course of individual infections. We show that prevalence can be accurately estimated across a broad range, from 0.02 to 20%, using only a few dozen pooled tests and using up to 400 times fewer tests than would be needed for individual identification. We then exhaustively evaluated the ability of different pooling designs to maximize the number of detected infections under various resource constraints, finding that simple pooling designs can identify up to 20 times as many true positives as individual testing with a given budget. Crucially, we confirmed that our theoretical results can be translated into practice using pooled human nasopharyngeal specimens by accurately estimating a 1% prevalence among 2304 samples using only 48 tests and through pooled sample identification in a panel of 960 samples. Our results show that accounting for variation in sampled viral loads provides a nuanced picture of how pooling affects sensitivity to detect infections. Using simple, practical group testing designs can vastly increase surveillance capabilities in resource-limited settings.
病毒学检测是严重急性呼吸综合征冠状病毒2(SARS-CoV-2)防控的核心,但许多地区在检测方面面临严重限制。混合检测提供了一种通过检测组合样本池来提高检测通量的方法;然而,大多数提议的设计尚未解决对灵敏度损失和实施可行性的关键担忧。在这里,我们结合了疫情传播的数学模型和SARS-CoV-2感染的经验性病毒动力学,以确定对流行率变化具有稳健性的混合设计,并验证针对个体感染时间进程的灵敏度损失。我们表明,仅使用几十次混合检测,就可以在0.02%至20%的广泛范围内准确估计流行率,且使用的检测次数比个体识别所需的检测次数少多达400倍。然后,我们详尽评估了不同混合设计在各种资源限制下最大化检测感染数量的能力,发现简单的混合设计在给定预算下能够识别出比个体检测多20倍的真阳性病例。至关重要的是,我们通过仅使用48次检测在2304个样本中准确估计出1%的流行率,并在一组960个样本中进行混合样本识别,证实了我们的理论结果可以通过使用人类鼻咽拭子样本转化为实际应用。我们的结果表明,考虑采样病毒载量的变化可以细致地呈现混合检测如何影响检测感染的灵敏度。使用简单、实用的混合检测设计可以极大地提高资源有限地区的监测能力。